This proposal requests support to continue a successful predoctoral and postdoctoral training program designed to provide training in molecular and cellular aspects of drug abuse research. The University of Washington School of Medicine has strong research programs studying molecular aspects of drug receptor signaling mechanisms in several departments, and this training program has dramatically facilitated the coordination of training and collaboration of research effort among the drug abuse researchers at this institution. Examples of ongoing studies include: signal transduction by opiate receptor tolerance, cannabinoid receptors signaling and tolerance, the development of novel opiate drugs, the regulation of ionic channels by psychotomimetic agents, the effects of drugs of abuse on G-protein coupled enzyme and channel activities, and the molecular consequences of chronic drug exposure. We expect that the continued application of increasingly sophisticated biochemical and physiological methods will provide important advances in our understanding of the mechanisms by which specific drugs of abuse act. It is the intent of this program to identify and support three predoctoral students and three postdoctoral fellows interested in studying molecular and cellular mechanisms of drug action of specific abused drugs. Graduate students in their second or third years of study who identify a thesis project of direct relevance to the research mission of NIDA (characterization of the actions of pharmacological agents subject to the non-medical use) will be supported and encouraged through this training program. Postdoctoral fellows similarly working on a research project of direct relevance will be supported. The training program will be strongly research oriented but will also include seminars, journal clubs and didactic presentations on broader issues relevant to the study of drug abuse. Beyond the directly beneficial effects on the careers of the trainees, one of the most significant successes of the previously funded program has been its catalytic effect on the research environment at this institution: it has provide a means to support new investigators (Mackie and Terman) who are establishing new programs in cannabinoid and opiate research; it has encouraged established investigators to expand their research on drug abuse (Storm, Nathanson, Tempel); it has provided a platform to bring the molecular scientists in better contact with the behavioral and clinical drug abuse researchers at this institution. Although this has been a relatively small program, it has had a big impact here, and its renewal would encourage the further development of the drug abuse research community here. A funded Drug Abuse Research Training Program will continue to serve as an important catalyst to focus research at this institution on the basic neurobiology of a significant health issue.